Tecoma plant based compositions for treating skin lesions

ABSTRACT

A plant-based composition containing an alcohol extract of Tecoma species (e.g. Tecoma stans) and an exogenous carrier and/or excipient. Also provided is a composition including a mixture of three acids, namely corosolic acid, oleanolic acid, and ursolic acid, which can be found in the Tecoma species. Methods of treating skin lesions (e.g. warts, corns, calluses, and umbilical granulomas) and reducing symptoms associated with the skin lesions using such compositions are specified.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalApplication No. 62/731,234 filed Sep. 14, 2018, the entire contents ofwhich are herein incorporated by reference.

BACKGROUND OF THE INVENTION Technical Field

The present disclosure relates to a composition including an alcoholextract of Tecoma species and an exogenous pharmaceutically acceptablecarrier and/or excipient. The present disclosure also relates to acomposition containing a mixture of corosolic acid, oleanolic acid, andursolic acid. These compositions are useful for treating superficiallesions including skin warts, calluses, corns, umbilical granuloma, andsuperficial basal cell carcinoma.

Description of the Related Art

The “background” description provided herein is for the purpose ofgenerally presenting the context of the disclosure. Work of thepresently named inventors, to the extent it is described in thisbackground section, as well as aspects of the description which may nototherwise qualify as prior art at the time of filing, are neitherexpressly or impliedly admitted as prior art against the presentinvention.

Conventional treatment of skin warts, calluses, and corns involves theuse of keratolytic agents (e.g. salicylic acid), and/or other invasivemedical procedures (e.g. cryosurgery, cryotherapy, and cauterization),which frequently leave scars in the treated skin area. In addition,there is no effective antiviral agent for curing skin lesions such aswarts, which are caused by human papilloma virus (HPV). Physical removalof warts does not eradicate the causative virus. Therefore, recurrencerate of warts after clinical cure is often high due to virusreinfection.

Currently available medications for skin infections caused by HPVinclude Imiquimod (INN), which is a prescription drug acting as animmune response modifier. However, INN only shows limited effectivenessagainst the infection and cannot be used during pregnancy.

Traditional therapies for umbilical granuloma include topicalapplication of a necrotic agent such as silver nitrate. However, largegranulomas and those which do not respond to silver nitrate treatmentmay require invasive procedures including surgical excision.

Therefore, improved treatments for these skin lesions that do notinvolve an invasive procedure are still needed. In view of the forgoing,one objective of the present disclosure is to provide a composition withTecoma plant extract. Another objective of the present disclosure is toprovide a formulation containing a mixture of corosolic acid, oleanolicacid, and ursolic acid. The composition and the formulation are botheffective for the treatment of skin lesions, in particular warts, corns,calluses, umbilical granulomas, and superficial basal cell carcinoma.

BRIEF SUMMARY OF THE INVENTION

A first aspect of the present disclosure relates to a plant-basedcomposition that contains 1-500 g/L of an alcohol extract of at leastone species of Tecoma relative to a total volume of the plant-basedcomposition, and an exogenous pharmaceutically acceptable carrier and/orexcipient which is not present in the at least one species of Tecoma,wherein the exogenous pharmaceutically acceptable carrier and/orexcipient is an organic solvent, a cream base, or both, with the provisothat the organic solvent is not a polar protic solvent.

In one embodiment, the at least one species of Tecoma is selected fromthe group consisting of Tecoma beckii, Tecoma capensis, Tecomacastanifolia, Tecoma cochabambensis, Tecoma fulva, Tecoma nyassae,Tecoma rosifolia, Tecoma stans, Tecoma tenuiflora, and Tecomaweberbaueriana.

In one embodiment, the at least one species of Tecoma is Tecoma stans.

In one embodiment, the exogenous pharmaceutically acceptable carrierand/or excipient is the cream base, and the cream base comprises atleast one selected from the group consisting of an emollient, anocclusive agent, and a thickener.

In one embodiment, the exogenous pharmaceutically acceptable carrierand/or excipient is DMSO.

In one embodiment, the alcohol extract of at least one species of Tecomais sourced from a leaf, a stem, and/or a bark.

In one embodiment, the alcohol extract of at least one species of Tecomais sourced from a leaf.

In one embodiment, the alcohol extract of at least one species of Tecomais a methanol extract, an ethanol extract, or both.

In one embodiment, the plant-based composition contains 10-100 g/L of analcohol extract of Tecoma stans relative to a total volume of theplant-based composition.

A second aspect of the present disclosure relates to a compositioncontaining (i) corosolic acid, (ii) oleanolic acid, and (iii) ursolicacid, wherein a weight ratio of corosolic acid to oleanolic acid is in arange of 1:2 to 2:1, a weight ratio of corosolic acid to ursolic acid isin a range of 1:2 to 2:1, and a total weight of corosolic acid,oleanolic acid, and ursolic acid is at least 50 wt % relative to a totalweight of the composition.

A third aspect of the present disclosure relates to a formulationinvolving the composition of the second aspect, and a pharmaceuticallyacceptable carrier and/or excipient, wherein corosolic acid, oleanolicacid, and ursolic acid are each present in an amount of 0.01-50 g/Lrelative to a total volume of the topical formulation.

In one embodiment, the pharmaceutically acceptable carrier and/orexcipient includes DMSO.

A fourth aspect of the present disclosure relates to a method fortreating a skin disease or condition. The method involves topicallyadministering an effective amount of the plant-based composition of thefirst aspect onto a subject in need of therapy.

In one embodiment, the skin disease or condition is at least oneselected from the group consisting of warts, corns, calluses, umbilicalgranulomas, and superficial basal cell carcinoma.

In one embodiment, the subject is administered with an effective amountof the plant-based composition 1 to 10 times daily for 1 to 30consecutive days.

A fifth aspect of the present disclosure relates to a method fortreating a skin disease or condition. The method involves topicallyadministering an effective amount of the formulation of the third aspectonto a subject in need of therapy.

In one embodiment, the skin disease or condition is at least oneselected from the group consisting of warts, corns, calluses, umbilicalgranulomas, and superficial basal cell carcinoma.

In one embodiment, the subject is administered with an effective amountof the formulation 1 to 10 times daily for 1 to 30 consecutive days.

A sixth aspect of the present disclosure relates to a personal careproduct containing the plant-based composition of the first aspect.

A seventh aspect of the present disclosure relates to a personal careproduct containing the composition of the second aspect.

The foregoing paragraphs have been provided by way of generalintroduction, and are not intended to limit the scope of the followingclaims. The described embodiments, together with further advantages,will be best understood by reference to the following detaileddescription taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete appreciation of the disclosure and many of the attendantadvantages thereof will be readily obtained as the same becomes betterunderstood by reference to the following detailed description whenconsidered in connection with the accompanying drawings, wherein:

FIG. 1A shows the chemical structure of Pheophorbide-a identified inTecoma stans.

FIG. 1B shows the chemical structure of benzylbenzoate identified inTecoma stans.

FIG. 1C shows the chemical structure of β-sitosterol identified inTecoma stans.

FIG. 1D shows the chemical structure of diisooctyl phthalate identifiedin Tecoma stans.

FIG. 1E shows the chemical structure of oleanolic acid identified inTecoma stans.

FIG. 1F shows the chemical structure of ursolic acid identified inTecoma stans.

FIG. 1G shows the chemical structure of luteolin 4′-methyl etheridentified in Tecoma stans.

FIG. 1H shows the chemical structure of β-sitosteryl glucosideidentified in Tecoma stans.

FIG. 1I shows the chemical structure of corosolic acid identified inTecoma stans.

FIG. 1J shows the chemical structure of apigenin identified in Tecomastans.

FIG. 1K shows the chemical structure of luteolin 3′-methyl etheridentified in Tecoma stans.

FIG. 1L shows the chemical structure of luteolin identified in Tecomastans.

FIG. 1M shows the chemical structure of acteoside identified in Tecomastans.

FIG. 1N shows the chemical structure of isoacteoside identified inTecoma stans.

FIG. 2A is a picture showing untreated human skin having warts.

FIG. 2B is a picture showing the human skin of FIG. 2A after treatmentwith a methanol extract of Tecoma stans twice daily for 7 days.

FIG. 2C is a picture showing the human skin of FIG. 2A 1 year aftertreatment with a methanol extract of Tecoma stans twice daily for 7days.

FIG. 3A is a picture showing untreated human skin having warts.

FIG. 3B is a picture showing the human skin of FIG. 3A 3 days aftertreatment with a mixture of corosolic acid, oleanolic acid, and ursolicacid twice daily.

FIG. 3C is a picture showing the human skin of FIG. 3A 7 days aftertreatment with a mixture of corosolic acid, oleanolic acid, and ursolicacid twice daily.

FIG. 4A is a picture showing untreated human skin having warts.

FIG. 4B is a picture showing the human skin of FIG. 4A 3 days aftertreatment with a mixture of corosolic acid, oleanolic acid, and ursolicacid twice daily.

FIG. 4C is a picture showing the human skin of FIG. 4A 5 days aftertreatment with a mixture of corosolic acid, oleanolic acid, and ursolicacid twice daily.

FIG. 5A is a picture showing untreated human skin having calluses.

FIG. 5B is a picture showing the human skin of FIG. 5A 3 days aftertreatment with a mixture of corosolic acid, oleanolic acid, and ursolicacid twice daily.

FIG. 6A is a picture showing untreated human skin having calluses.

FIG. 6B is a picture showing the human skin of FIG. 6A 5 days aftertreatment with a methanol extract of Tecoma stans twice daily.

FIG. 7A is a picture showing untreated infant skin having umbilicalgranulomas.

FIG. 7B is a picture showing the infant skin of FIG. 7A 3 days aftertreatment with a methanol extract of Tecoma stans twice daily.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Embodiments of the present disclosure will now be described more fullyhereinafter with reference to the accompanying drawings, in which some,but not all embodiments of the disclosure are shown.

As used herein, the words “a” and “an” and the like carry the meaning of“one or more”. Within the description of this disclosure, where anumerical limit or range is stated, the endpoints are included unlessstated otherwise. Also, all values and subranges within a numericallimit or range are specifically included as if explicitly written out.

The first aspect of the present disclosure relates to an plant-basedcomposition, comprising, consisting essentially of, or consisting of:1-500 g/L, 5-400 g/L, 10-300 g/L, 20-200 g/L, or 50-100 g/L of analcohol extract of at least one species of Tecoma relative to a totalvolume of the plant-based composition, and an exogenous pharmaceuticallyacceptable carrier and/or excipient which is not present in the at leastone species of Tecoma, wherein the exogenous pharmaceutically acceptablecarrier and/or excipient is an organic solvent, a cream base, or both,with the proviso that the organic solvent is not a polar protic solvent.

As used herein, “plant” or “plant part” refers to any living organism ofthe kingdom Plantae and includes all plants described as grains, fruitsand vegetables as well all plant parts or components including, but notlimited to, roots, leaves, barks, branches, seeds, stems, stem shoots,bulbs, nuts, beans, grains, flowers, flower bud, pollen, vegetableskins, fruits and fruit skins during all periods of growth, preferablyflowers, roots, barks, fruits, stems, and leaves during all periods ofgrowth. Plant extracts, as defined herein, include solvent (e.g. aqueousand alcoholic) extracts obtained from any of the plant parts such as theflowers, roots, barks, fruits, stems, and leaves, as well as the wholeplant. Extracts of Tecoma stans leaf are especially preferred. The plantextract comprises phytochemicals and/or metabolites that include,without limitation, alkaloids, flavonoids, saponins, carbohydrates,polysaccharides, terpenoids (e.g., monoterpenoids and sesquiterpenoids),steroids, sterols, phenols, tannins, anthraquinones, anthocyanins, aminoacids, proteins, and vitamins.

The at least one species of Tecoma may be Tecoma beckii, Tecomacapensis, Tecoma castanifolia, Tecoma cochabambensis, Tecoma fulva,Tecoma nyassae, Tecoma rosifolia, Tecoma stans, Tecoma tenuiflora,Tecoma weberbaueriana, or combinations thereof. Hybrid types such asTecoma x smithii may be used as a species of Tecoma. A hybrid namecontains “x” which links the parents of the hybrid. In at least oneembodiment, the plant-based composition is substantially free of Tecomaavellanedae. Tecoma avellanedae, also referred to as Handroanthusimpetiginosus, which belongs to a different genus than the Tecomaspecies of the present disclosure.

In a preferred embodiment, the at least one species of Tecoma is Tecomastans. Tecoma stans (yellow bells, yellow trumpetbush) is a perennialshrub in the trumpet vine family that is cultivated as an ornamentalplant. It has sharply toothed, lanceolate shaped, pinnate green leavesand bears large, showy, bright golden yellow trumpet-shaped flowers. Theplant grows well in warm climates. Traditionally, Tecoma stans is knownfor its antidiabetic effects and is widely used in south America,southeast Asia, and the east coast of the United States for treatingdiabetes. A concentrated decoction of the flowers and leaves of Tecomastans may be taken orally as an antidiabetic medication. In the ArabianGulf peninsula, concentrated decoctions of the plant have been appliedtopically onto the skin for treating eczema. Extracts of Tecoma stanshave been tested for their anti-proliferative, antioxidant,anti-inflammatory, central analgesic, anti-nociceptive, antispasmodic,cardio-protective, antimicrobial (e.g. antibacterial, antifungal),insecticidal, wound healing, antidiabetic, nephroprotective andhepatoprotective effects as well as gastric ulcer healing properties[Amad M al-Lazzari (2012); Genotoxic and Cytotoxic study of Tecoma stansBignoniaceae; Pakistan journal of biological sciences; Vol. 15 No. 2;92-97; Anburaj G., Marimuthu M. and Manikandan R (2016); In vitroantimicrobial activity of aqueous and Ethanol extracts of Tecoma stansbark against pathogenic Bactria; International Recent Research Journalon Science and Technology; Vol. 8 No. 2; 26-28; Anburaj G., MarimuthuM., Rajasudha V. and Manikandan R (2016); Phytochemical screening andGC-MS analysis of ethanolic extract of Tecoma stans (Family:Bignoniaceae) Yellow Bell Flowers; Journal of Pharmacognosy andPhytochemistry; Vol. 5 No. 4; 172-175; Anburaj G., Marimuthu M.,Sobiyana P. and Manikandan R. (2016); A Review on Tecoma stans;International Journal of Engineering Research and Modern Education; Vol.1 No. 1; 43-49; Arnabaditya Mohanty, Vinod Kumar Sahu, Ashutosh Mishra,Dusmanta Kumar Pradhan and Manas Ranjan Mishra (2012); Gastric ulcerhealing activity of Tecoma stans Leaf; International Research Journal ofPharmaceutical Sciences; Vol. 3 No. 1; 32-33; Boopathi T.,Gopalasatheeskumar K., Parthiban S., Sangeetha G., Thanga Kokila M. andManimaran T (2017); Evaluation of Antimicrobial Activity of Tecoma stansand Muntingia calabura; World Journal of Pharmaceutical Research; Vol. 6No. 3; 617-627; Brahmam B., Sirisha K., Sathish Kumar M., Narendra BabuA. and Rama Rao N. V (2015); Evaluation of Central Analgesic Activity ofTecoma stans Flower Extracts; Vol. 4 No. 1; 89-92; Brahmam B., SirishaK., Sathish Kumar M., Narendra Babu A., Rama Rao N. V. and Rama Rao N(2015); Evaluation of Anti-inflammatory Activity of Flower Extracts ofTecoma stans on Carrageenan-Induced Paw oedema in Rats by Using DigitalPlethysmometer; Research Journal of Pharmaceutical, Biological andChemical Sciences; Vol. 6 No. 5; 641-644; Chaugan S. V. S., Jolly Singhand Satoshi Tahara (2004); Role of phenolic sans boron in reproductivesuccess in seasonally transient sterile Tecoma stans L; Indian journalof experimental biology; Vol. 42 No. 1; 197-201; Das C., Dash S., SahooD. C. and Mohanty A (2010); Evaluation of Methanolic Bark Extract ofTecoma stans Linn, for Wound Healing in Albino Rats; InternationalJournal of Pharmacy and Technology; Vol. 2 No. 3; 735-742; Divya Sri G.,Narendra Babu A., Sathish Kumar M., Venkateswarlu V. and Ashok Kumar K(2014); Pharmacognostical Characteristics and Medicinal Uses of Tecomastans: A Review; Journal of Medical and Pharmaceutical Innovation; Vol.1 No. 2; 1-4; Gharib Naseri M. K., Asadi Moghaddam M. and Bahadoram S(2007); Antispasmodic effect of Tecoma stans (L.) Juss leaf extract onrat ileum; DARU; Vol. 15 No. 3; 123-128; Govindappa M., Sadananda T. S.,Channabasava R. and Vinay B Raghavendra (2011); In vitroAnti-Inflammatory, Lipoxygenase, Xanthine Oxidase andAcetylcholinesterase Inhibitory Activity of Tecoma stans (L.) Juss. ExKunth; International Journal of Pharma and Bio Sciences; Vol. 2 No. 2;275-285; Govindappa M., Sadananda T. S., Channabasava R., Jeevitha M.K., Pooja K. S., Vinay B. and Raghavendra (2011) Antimicrobial,Antioxidant Activity and Phytochemical Screening of Tecoma stans (L.)Juss. Ex Kunth; Journal of Phytology Phyto-pharmacology; Vol. 3 No. 3;68-76; Indra Gandhi M. and Ramesh S (2010); Antifungal and hemolyticactivities of organic extracts of Tecoma stans (Bignoniaceae); Journalof Ecobiotechnology; Vol. 2 No. 2; 26-32; Kameshwaran S., SenthilkumarR., Thenmozhi S. and Dhanalakshmi M (2014); Wound healing potential ofethanolic extract of Tecoma stans flowers in rat; Pharmacologia; Vol. 1No. 1; 215-221; Kameshwaran S., Sundaraganapathy R., Thenmozhi S.,Dhanalakshmi M., Vasuki K. and Manjuladevi K (2014); Tecoma stansprotect Central Nervous System Against Oxidative Damages ofElectromagnetic Radiation on Rat; Acta Biomedica Scientia; Vol. 1 No. 1;40-44; Kameshwaran S., Suresh V., Arunachalam G., Kanthlal S. K. andMohanraj M (2012); In vitro and in vivo anti-cancer activity ofmethanolic extract of Tecoma stans flowers; International researchjournal of pharmacy; Vol. 3 No. 3; 246-251; Kamilia F. Taha, El-sayedaA. El-kashoury, Shahira M. Ezzat and Naglaa A. Saleh (2016);Antimicrobial and antioxidant activity of volatile constituents of theleaves of Tecoma Smithii Will Wats; Global Journal of Medicinal PlantResearch; Vol. 4 No. 4; 16-22; Kottai Muthu A., Borse L. B.,Thangatripathi A. and Borse S. L (2012); Antioxidant activity ofheartwood of Tecoma stans. (L) Juss. Ex Kunth; Journal of PharmacyResearch; Vol. 5 No. 2; 896-898; Kottai Muthu A., Laxmikant B. Borse,Thangatripathi A. and Sandhya L. Borse (2012); Antimicrobial Activity ofHeartwood of Tecoma stans; International Journal of Pharmacy andPharmaceutical Sciences; Vol. 4 No. 3; 384-386; Lakshmi Prasanna V.,Lakshman K., Medha M. Hegde and Vinutha Bhat (2013); Antinociceptive andAnti-Inflammatory activity of Tecoma stans Leaf Extracts; Indian Journalof Research in Pharmacy and Biotechnology; Vol. 1 No. 2; 156-160;Mohamed Abdel-Hamid Taher, Dawood Hosni Dawood, Mostafa Ibrahim Sanadand Ramadan Ahmed Hassan (2016); Searching for anti-hyperglycemicphytomolecules of Tecoma stans; European Journal of Chemistry; Vol. 7No. 4; 397-404; Name H. and Minal Wani (2014); Callus Induction Studiesand Active Components and Antioxidant Activity Investigation from Leavesand Callus of Tecoma stans L. Juss. Ex Kunth; Research Journal ofPharmaceutical, Biological and Chemical Sciences; Vol. 5 No. 2; 604-610;Rajamurugan R., Thirunavukkarasu C., Sakthivel V., Sivashanmugam M. andRaghavan C. M (2013); Phytochemical Screening, Antioxidant andAntimicrobial Activities of Ethanolic Extract of Tecoma stans Flowers;Int J Pharm Bio Sci.; Vol. 4 No. 2; 124-130; Raju S., Kavimani S., UmaMaheshwara Rao V. and Sreeramulu Reddy K (2011); Tecoma stans (L.) Juss.ex Kunth (Bignoniaceae): Ethnobotany, Phytochemistry and Pharmacology;Journal of Pharmaceutical and Biomedical Sciences; Vol. 8 No. 7; 1-5;Ramesh T., Anusha V. and Ravi Kumar (2009); Antibacterial Activity ofMethanolic Extract of Roots of Tecoma stans; Int. J. Chem. Sci.; Vol. 7No. 1; 6-8; Senthilkumar C. S., Suresh Kumar M. and Rajasekara Pandian M(2010); In vitro Antibacterial Activity of Crude Leaf Extracts fromTecoma stans (L) Juss. Et Kunth, Coleus Forskohlii and PogostemonPatchouli against Human Pathogenic Bacteria; International Journal ofPharmTech Research; Vol. 2 No. 1; 438-442; Shanmukha I., AbubakerSiddiq, Prabhu K. and Ramachandra Setty S (2012); Effect of Tecoma stansLeaves Extract on Experimentally Induced Renal Injury In Various AnimalModels; Am. J. PharmTech Res.; Vol. 2 No. 6; 800-809; Shanmukha I.,Vijay Kumar M. and Ramachandra Setty S (2013); Effect of Tecoma stansLeaves for its Preventive Role on Experimentally Induced Liver Toxicity;International Journal of Pharm Tech Research; Vol. 5 No. 3; 915-923;Shanmukha I., Vijay Kumar M. and Ramachandra Setty S (2014);Cardioprotective effect of hydroalcoholic extract of Tecoma stansflowers against isoproterenol-induced myocardial infarction in rats;Asian Pac J Trop Dis.; Vol. 4 No. 1; 378-384; Sridharan G., Sarvanan R.and Brindha P (2014); Evaluation of Anticancer Potentials of Tecomastans (L). Juss. Ex. Kunth against EAC Cell Lines; International Journalof Pharmacy and Pharmaceutical Sciences; Vol. 6 No. 1; 88-92;Subalakshmi T. and Jepa Chandra Mohan (2017); Inhibitory Effect ofDifferent Solvent Extracts of Tecoma stans, Ixora Coccinea and AervaLenata Leaves on Pseudomonas aeruginosa and Streptococcus Sp. of cattlePathogens; World Journal of Pharmacy and Pharmaceutical Sciences; Vol. 6No. 2; 1219-1228; Sundas Iltaf, Zaheer-Ud-Din Khan, Rizwana Rafique andAnjum Parveen (2016); Evaluation of antibacterial activity of leafextracts of Mansoa alliacea (Lam.), Tecomaria capensis (Thunb.) Spachand Tecoma stans (L.) Juss. Ex; Journal of Biodiversity andEnvironmental Sciences; Vol. 9 No. 1; 69-75; Sunitha Katta, GanapathySeru and Sridhar Y (2016); Constituents from the Leaves of Tecoma stansJuss; World Journal of Pharmaceutical Sciences; Vol. 4 No. 12; 272-274;Sunita Verma (2016); Phytochemical and pharmacological review study onTecoma stans Linn; Journal of Medicinal Plants Studies; Vol. 4 No. 5;162-164; Tavs A. Abere and Comfort O. Enoghama (2015); Pharmacognosticstandardization and insecticidal activity of the leaves of Tecoma stansJuss (Bignoniaceae); Journal of Science and Practice of Pharmacy; Vol. 2No. 1; 39-45; and Thirumal M., Kishore G. and Surya Srimanthula (2013);Anti-Proliferative Activity of Various Parts of Tecoma stans (L.)Against Human Breast Cancer Cells In vitro; Research Journal ofPharmaceutical, Biological, and Chemical Sciences; Vol. 4 No. 2;305-313].

The alcohol extract of Tecoma may be sourced from a leaf, a stem, abark, or combinations thereof. Preferably, the alcohol extract of Tecomais sourced from a leaf. In some embodiments, the alcohol extract ofTecoma is not sourced from a flower, a root, and a fruit. As discussedin Example 1, extracts from the flower, the root, and the fruit fromTecoma stans exhibited much lower therapeutic effect than that from theleaf.

Exemplary alcohols include, but are not limited to, methanol, ethanol,trifluoroethanol, n-propanol, i-propanol, n-butanol, i-butanol,t-butanol, n-pentanol, i-pentanol, 2-methyl-2-butanol,2-trifluoromethyl-2-propanol, 2,3-dimethyl-2-butanol, 3-pentanol,3-methyl-3-pentanol, 2-methyl-3-pentanol, 2-methyl-2-pentanol,2,3-dimethyl-3-pentanol, 3-ethyl-3-pentanol, 2-methyl-2-hexanol,3-hexanol, cyclopropylmethanol, cyclopropanol, cyclobutanol,cyclopentanol, cyclohexanol, and polyols (e.g. propylene glycol,polyethylene glycol, glycerol, and poly(tetramethylene ether) glycol).

In some embodiments, the alcohol extract of Tecoma is a methanolextract, an ethanol extract, an n-propanol extract, an isopropanolextract, an n-butanol extract, or mixtures thereof. In a preferredembodiment, the alcohol extract of Tecoma is a methanol extract, anethanol extract, or both. Most preferably, the alcohol extract of Tecomais a methanol extract. In certain embodiments, other solvents including,but not limited to, water, acetone, acetonitrile, tetrahydrofuran (THF),1,4-dioxane, dichloromethane, chloroform, ethyl acetate, pet ether,pentane, hexane(s), may be used in addition to or in lieu of the alcoholto extract the Tecoma.

Solvent extraction methods of plants are known to those of ordinaryskill in the art. For example, the alcohol extracts of the presentdisclosure may be prepared as follows. The plant part(s) of interest maybe collected and then washed thoroughly, preferably twice/thrice withtap water, to remove both epiphytes and necrotic plants; preferablyfollowed by washing with sterile distilled water to remove associateddebris if any. The clean and fresh plant parts may be sun-dried or driedin the shade for 5-60 days, preferably 10-40 days, or about 30 days, andthen finely cut, or preferably powdered/pulverized. The dried finely cutor powdered plant parts may be mixed and extracted with the alcohol(e.g., methanol) in an amount of 0.001-5 g/mL, 0.01-3 g/mL, 0.02-2 g/mL,or 0.1-1 g/mL of the alcohol at a temperature of 10-50° C., 15-40° C.,or 20-30° C. for 0.5-30 days, preferably 1-20 days, more preferably 5-10days. The resulting infusion is then preferably filtered thoroughlyuntil no insoluble material appears in the alcohol extract to obtain adiluted alcohol extract. The diluted alcohol extract may be concentratedvia evaporation of the alcohol by heating under standard pressure,drying under vacuum, and/or using a rotary evaporator. In someembodiments, the alcohol content of the alcohol extract of Tecoma isless than 10 wt %, preferably less than 5 wt %, more preferably lessthan 2 wt %, relative to a total weight of the alcohol extract.

The alcohol extract of the at least one species of Tecoma may comprisemacrocyclic compounds including Pheophorbide-a (FIG. 1A), pentacyclictriterpenoids including oleanolic acid (FIG. 1E), ursolic acid (FIG.1F), and corosolic acid (FIG. 1I), esters including benzylbenzoate (FIG.1B), and diisooctyl phthalate (FIG. 1D), phytosterols and derivativesthereof including β-sitosterol (FIG. 1C), and β-sitosteryl glucoside(FIG. 1H), flavonoids including luteolin (FIG. 1L), luteolin 4′-methylether (FIG. 1G), luteolin 3′-methyl ether (FIG. 1K), apigenin (FIG. 1J),as well as caffeoyl phenylethanoid glycosides including acteoside(verbascoside) (FIG. 1M), and andisoacteoside (FIG. 1N).

In some embodiments, the plant-based composition contains 0.1-500 g/L ofthe alcohol extract of at least one species of Tecoma relative to atotal volume of the plant-based composition, preferably 0.5-400 g/L,preferably 1-300 g/L, preferably 5-200 g/L, preferably 10-100 g/L,preferably 15-80 g/L, preferably 20-60 g/L, preferably 30-50 g/L of thealcohol extract of at least one species of Tecoma relative to a totalvolume of the plant-based composition. In a preferred embodiment, theplant-based composition contains 0.1-500 g/L of the alcohol (e.g.methanol) extract of Tecoma stans relative to a total volume of theplant-based composition, preferably 0.5-400 g/L, preferably 1-300 g/L,preferably 5-200 g/L, preferably 10-100 g/L, preferably 15-80 g/L,preferably 20-60 g/L, preferably 30-50 g/L of the alcohol extract ofTecoma stans relative to a total volume of the plant-based composition.

The term “carrier” encompasses any excipient, binder, diluent, filler,salt, buffer, solubilizer, lipid, stabilizer, or other material wellknown in the art for use in pharmaceutical formulations. The choice of acarrier for use in a composition will depend upon the intended route ofadministration for the composition. The preparation of pharmaceuticallyacceptable carriers and formulations containing these materials isdescribed in, e.g. Remington's Pharmaceutical Sciences, 21st Edition,ed. University of the Sciences in Philadelphia, Lippincott, Williams &Wilkins, Philadelphia Pa., 2005, which is incorporated herein byreference in its entirety). Examples of physiologically acceptablecarriers include antioxidants including ascorbic acid; low molecularweight (less than about 10 residues) polypeptides; proteins, such asserum albumin, gelatin, or immunoglobulins; hydrophilic polymers such aspolyvinylpyrrolidone; amino acids such as glycine, glutamine,asparagine, arginine or lysine; monosaccharides, disaccharides, andother carbohydrates including glucose, mannose, or dextrins; chelatingagents such as EDTA; sugar alcohols such as mannitol or sorbitol;salt-forming counterions such as sodium; and/or nonionic surfactantssuch as TWEEN® (ICI, Inc.; Bridgewater, N.J.), polyethylene glycol(PEG), and PLURONICS™ (BASF; Florham Park, N.J.). An “excipient” refersto an inert substance added to a composition to further facilitateadministration of a compound. Examples, without limitation, ofexcipients include calcium carbonate, calcium phosphate, various sugarsand types of starch, cellulose derivatives, gelatin, vegetable oils, andpolyethylene glycols.

As used herein, the term “pharmaceutically acceptable” refers tocounter-ions, compounds, materials, ingredients, compositions, and/ordosage forms which are, within the scope of sound medical judgement,suitable for use in contact with the tissues (e.g. skin) of human beingsand animals without excessive toxicity, irritation, allergic response,or other problem or complication, commensurate with a reasonablebenefit/risk ratio.

The plant-based composition further comprises an exogenouspharmaceutically acceptable carrier and/or excipient which is notpresent in the at least one species of Tecoma. The exogenouspharmaceutically acceptable carrier and/or excipient may be an organicsolvent that is not a polar protic solvent, a cream base, or both. Whenpresent, the cream base may contain at least one selected from the groupconsisting of an emollient, an occlusive agent, and a thickener. Thefollowing carriers and excipients are not found in Tecoma.

Exemplary organic solvent that may be applicable to the presentdisclosure include, but are not limited to, alkyl methyl sulfoxide(e.g., dimethyl sulfoxide (DMSO), decylmethyl sulfoxide,tetradecylmethyl sulfoxide), glycol ethers (e.g. 1,2-dimethoxyethane,diglyme, triglyme), ketones (e.g., acetone, butanone), esters (e.g.ethyl acetate, propyl acetate), an amide/lactam (e.g. dimethylformamide,dimethylacetamide, N-methyl-2-pyrrolidone), acetonitrile, propionitrile,butyronitrile, benzonitrile, ethylene carbonate, propylene carbonate,1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, pentane, hexane,heptane, diethyl ether, 1,4-dioxane, and mixtures thereof. In at leastone embodiment, the organic solvent is not a polar protic solvent suchas methanol, ethanol, n-propanol, isopropanol, and n-butanol.

In a preferred embodiment, the exogenous pharmaceutically acceptablecarrier and/or excipient is dimethyl sulfoxide (DMSO). DMSO is aversatile substance that has numerous pharmaceutical and cosmetic uses.For example, DMSO may be effective in boosting tissue (e.g. skin)penetration of other substances it carries, especially othertherapeutically active ingredient, and thus accelerate delivery andassimilation of a pharmaceutical/cosmetic composition into the tissue.If present, DMSO may be present in the plant-based composition in anamount of 1-1,000 g/L, 10-750 g/L, 25-500 g/L, 50-250 g/L, or 100-200g/L.

An emollient may attract and hold water in the stratum corneum andepidermis after topic application of the plant-based composition.Exemplary emollients include, without limitation, urea, aloe vera gel,an α-hydroxy acid (e.g., lactic acid), glyceryl triacetate, a polymericpolyol (e.g., polydextrose), a sugar alcohol (e.g., glycerol/glycerin,sorbitol, xylitol, and maltitol), a PEG-20 almond glyceride, GlucamP-20, Glucam E-10, Glucam P-10, Glucam E-20, Glucam P-20 distearate,cetyl acetate, acetylated lanolin alcohol (e.g., acetulan), cetyl ether(e.g., PPG-10), myristyril ether (e.g., PPG-3), hydroxylated milkglycerides (e.g., Cremeral HMG), polyquaternium compounds (e.g., U-carecompounds), copolymers of dimethyl dialyl ammonium chloride and acrylicacid (e.g., Merquat), dipropylene glycol methyl ethers (e.g., DowanolDPM, Dow Corning), and polypropylene glycol ethers (e.g., Ucon50-HB-600, Union Carbide). Other suitable emollients may includehydrocarbon-based emollients, such as petrolatum or mineral oil; fattyester-based emollients, such as methyl, isopropyl and butyl esters offatty acids (e.g., isopropyl palmitate, isopropyl myristate, isopropylisostearate, diisopropyl sebacate); and C₁₂-C₁₆ fatty alcohol lactates,such as cetyl lactate and lauryl lactate. Additional fatty ester-basedemollients include isostearyl isostearate, propylene dipelargonate,2-ethylhexyl isononoate, 2-ethylhexyl stearate, isopropyl lanolate,2-ethylhexyl salicylate, cetyl myristate, oleyl myristate, oleylstearate, oleyl oleate, hexyl laurate, and isohexyl laurate. Additionaluseful emollients include lanolin, olive oil, cocoa butter, and sheabutter. If present, the emollient may be present in the plant-basedcomposition in an amount of 1-100 g/L, 5-80 g/L, 10-60 g/L, or 15-30g/L.

An occlusive agent may help create a semi-occlusive film on skin aftertopical application which can help form a barrier to inhibit evaporativeloss of moisture from the body and protect the skin from environmentalirritants. Exemplary occlusive agents include, but are not limited to,dimethicone, cyclomethicone, trimethylsiloxysilicate, and petrolatum. Ifpresent, the occlusive agent may be present in the plant-basedcomposition in an amount of 1-100 g/L, 5-80 g/L, 10-60 g/L, or 15-30g/L.

A thickening agent may assist in adjusting/enhancing the viscosity ofthe plant-based composition. Certain thickening agents may also functionas stabilizers to maintain the stability of an emulsion. Exemplarythickening agents include, but are not limited to, polyacrylamidepolymers, polysaccharides, natural or synthetic gums, such as methylhydroxypropyl cellulose, xanthan gum, polysaccharide gum, hydroxylpropyl cellulose, hydroxyl propyl methyl cellulose, and hydroxyl ethylcellulose. Some emollients, such as petrolatum, may also function as athickening agent. If present, the thickening agent may be present in theplant-based composition in an amount of 0.1-50 g/L, 0.5-25 g/L, 1-10g/L, or 2-5 g/L.

In some embodiments, the plant-based composition further comprises anemulsifier. Useful emulsifiers include ethoxylated fatty alcohols,ethoxylated fatty acids, partial glycerides of ethoxylated fatty acids,polyglycerolated fatty acid triglycerides and ethoxylated derivativesthereof, and mixtures thereof. Exemplary emulsifiers include, but arenot limited to, glyceryl stearate, cetyl alcohol, behenyl alcohol,cetearyl alcohol, stearic acid, and emulsifying waxes (e.g. Incroquatand Polawax). Surfactants may act as emulsifiers. Surfactants that maybe present in the plant-based compositions of the present disclosureinclude zwitterionic (amphoteric) surfactants, e.g.,phosphatidylcholine, and3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS),anionic surfactants, e.g., sodium lauryl sulfate, sodium octanesulfonate, sodium decane sulfonate, and sodium dodecane sulfonate,non-ionic surfactants, e.g., sorbitan monolaurate, sorbitanmonopalmitate, sorbitan trioleate, polysorbates such as polysorbate 20(Tween 20), polysorbate 60 (Tween 60), and polysorbate 80 (Tween 80),cationic surfactants, e.g., decyltri methyl ammonium bromide,dodecyltrim ethyl ammonium bromide, tetradecyltrimethylammonium bromide,tetradecyltrimethyl-ammonium chloride, and dodecylammonium chloride, andcombinations thereof. If present, the emulsifier may be present in theplant-based composition in an amount of 1-100 g/L, 5-80 g/L, 10-60 g/L,or 15-30 g/L.

In some embodiments, the plant-based composition further compriseswater, and/or an organic solvent in the cream base. Exemplary organicsolvents include, without limitation, ethers (e.g. diethyl ether,dibutyl ether, tetrahydrofuran, 1,4-dioxane, tetrahydropyran, t-butylmethyl ether, cyclopentyl methyl ether, di-iso-propyl ether), aromaticsolvents (e.g. benzene, o-xylene, m-xylene, p-xylene, and mixtures ofxylenes, toluene, mesitylene, anisole, 1,2-dimethoxybenzene,α,α,α,-trifluoromethylbenzene, fluorobenzene), hydrocarbons (e.g.,cyclohexane, hexane, isooctane, n-pentane), chlorinated solvents(dichloromethane, chloroform, carbon tetrachloride, perchloroethylene(tetrachloroethylene), 1,1,2,2-tetrachloroethane, 1,1,2-trichloroethane,trichloroethylene, methyl chloroform (1,1,1-trichloroethane),1,2,3-trichloropropane, ethylene dichloride, 1,2-dichloropropane(propylene dichloride), 1,2-dichloroethylene, 1,1-dichloroethane,chlorobenzene), alkyl methyl sulfoxide (e.g., dimethyl sulfoxide (DMSO),decylmethyl sulfoxide, tetradecylmethyl sulfoxide), glycol ethers (e.g.1,2-dimethoxyethane, diglyme, triglyme), ketone (e.g., acetone,butanone), esters (e.g. ethyl acetate, propyl acetate), an amide/lactam(e.g. dimethylformamide, dimethylacetamide, pyrrolidone,N-methyl-2-pyrrolidone, N-(2-hydroxyethyl) pyrrolidone), acetonitrile,propionitrile, butyronitrile, benzonitrile, ethylene carbonate,propylene carbonate, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone,and mixtures thereof.

The plant-based composition may be suitable for topical application. Theplant-based composition intended for topical application can be producedin liquid or semi-solid formulation. The composition may be in a form ofa salve, a lotion, a cream, an ointment, a solution, an emulsion, asuspension, a gel (e.g., a cream gel or a hydrogel), or asuspension/dispersion. In other embodiments, the composition may be in aform of a multiple emulsion, such as oil and/or silicone in wateremulsions, water-in-oil and/or silicone emulsions, water/oil/water orwater/silicone/water type emulsions, and oil/water/oil orsilicone/water/silicone type emulsions. The composition may be aleave-on type or a rinse-off type.

In some embodiments, the plant-based composition may be formulated foradministration by mouth. Solid dosage forms for oral administration caninclude capsules, tablets, pills, powders, and granules. Liquid dosageforms for oral administration can include pharmaceutically acceptableemulsions, solutions, suspensions, syrups, and elixirs containing inertdiluents commonly used in the art, such as water.

The plant-based composition may be prepared by mixing the aforementionedalcohol extract of at least one species of Tecoma and the exogenouspharmaceutically acceptable carrier and/or excipient such as DMSO,and/or the cream base (e.g. the emollient, the occlusive agent, thethickener, the emulsifier) simultaneously or sequentially. The mixingprocess may be performed in any conventional vessel with adequateagitation. In some embodiment, mixing is performed in a high speeddouble-mounted turbine dissolver. Methods of agitation include, but arenot limited to, using a propeller, using an agitator, a vortexer, arotary shaker, a magnetic stirrer, an overhead stirrer, a sonicator(e.g. an ultrasonic bath, an ultrasonic probe), and a pump.

A further aspect of the present disclosure relates to a compositioncomprising, consisting essentially of, or consisting of: (i) corosolicacid, (ii) oleanolic acid, and (iii) ursolic acid. A total weight ofcorosolic acid, oleanolic acid, and ursolic acid is at least 50 wt %,preferably at least 60 wt %, preferably at least 75 wt %, preferably atleast 80 wt %, preferably at least 90 wt %, preferably at least 95 wt %,preferably at least 98 wt %, preferably at least 99 wt %, relative to atotal weight of the composition. The composition of the presentdisclosure may be considered as a “concentrate” of the three acids (i.e.corosolic acid, oleanolic acid, ursolic acid).

In one embodiment, a weight ratio of corosolic acid to oleanolic acid isin a range of 1:2 to 2:1, preferably 2:3 to 3:2, more preferably about1:1. In a related embodiment, a weight ratio of corosolic acid toursolic acid is in a range of 1:2 to 2:1, preferably 2:3 to 3:2, morepreferably about 1:1.

The present disclosure is further intended to include compositions thatcontain single compound, or up to two compounds selected from the groupconsisting of (i) corosolic acid, (ii) oleanolic acid, and (iii) ursolicacid. For example, the composition may only contain corosolic acid,oleanolic acid, or ursolic acid in an amount of at least 50 wt %,preferably at least 60 wt %, preferably at least 75 wt %, preferably atleast 80 wt %, preferably at least 90 wt %, preferably at least 95 wt %,preferably at least 98 wt %, preferably at least 99 wt %, relative to atotal weight of the composition. Alternatively, the composition maycontain a mixture of corosolic acid and oleanolic acid, a mixture ofoleanolic acid and ursolic acid, or a mixture of corosolic acid andursolic acid in a ratio as previously specified, and in an amount of atleast 50 wt %, preferably at least 60 wt %, preferably at least 75 wt %,preferably at least 80 wt %, preferably at least 90 wt %, preferably atleast 95 wt %, preferably at least 98 wt %, preferably at least 99 wt %,relative to a total weight of the composition.

Triterpenes are a class of chemical compounds composed of three terpeneunits with the molecular formula C₃₀H₄₈. Triterpenoids arefunctionalized triterpenes having heteroatoms. Triterpenoids withseveral pentacyclic motifs may possess potential biological andmedicinal effects. Exemplary triterpenoids include, but are not limitedto, oleanolic acid, ursolic acid, betulinic acid, moronic acid,curcurbitacins, lupeol, and corosolic acid.

Corosolic acid (FIG. 1i , (2α,3β)-2,3-dihydroxyurs-12-en-28-oic acid,2α-hydroxyursolic acid) is a pentacyclic triterpene acid isolated fromthe leaves of Lagerstroemia speciosa. Lagerstroemia Speciosa is commonlyknown as Crepe Myrtle and belongs to the botanical family lythraceae. Itis a very common ornamental deciduous tree that grows in the tropicalareas of the globe. Corosolic acid has also been found in other plantssuch as Vacciniurn macrocarpon (cranberry), Ugni molinae, Eriobotryajaponica, Perilla frutescens, Weigela subsessilis, Glechoma longituba,Potentilla chinensis, Rubus biflorus, and Phlomis umbrosa. Corosolicacid has been previously studied for its use for controlling blood sugarlevels and treating diabetes. In some embodiments, the corosolic acid ofthe present disclosure is sourced from at least one species of Tecoma,preferably from Tecoma stans. Alternatively, corosolic acid may becommercially available from vendors such as Sigma-Aldrich.

Ursolic acid (FIG. 1F, 3β-Hydroxy-12-ursen-28-ic acid, urson, prunol,malol) is another pentacyclic triterpene acid present in many plants. Itcan be found in fruits and herbs such as apples, basil, bilberries,cranberries, peppermint, rosemary, lavender, oregano, thyme, hawthorn,and prunes. Ursolic acid has been investigated for its potentialanti-cancer effects. In some embodiments, the ursolic acid of thepresent disclosure is sourced from at least one species of Tecoma,preferably from Tecoma stans. Alternatively, ursolic acid may becommercially available from vendors such as Sigma-Aldrich, AcrosOrganics, TCI America, Spectrum Chemicals, and Enzo Life Sciences.

Oleanolic acid (FIG. 1E, oleanic acid) is also a naturally occurringpentacyclic triterpenoid. It can be found in olive oil, Phytolaccaamericana (American pokeweed), Syzygium spp, and garlic. Oleanolic acidhas been researched for its anti-HIV and anti-HCV activities. In someembodiments, the oleanolic acid of the present disclosure is sourcedfrom at least one species of Tecoma, preferably from Tecoma stans.Alternatively, oleanolic acid may be commercially available from vendorssuch as Sigma-Aldrich, Acros Organics, Alfa Aesar, and MP Biomedicals.

The present disclosure also relates to a formulation involving theaforementioned composition, and a pharmaceutically acceptable carrierand/or excipient, wherein corosolic acid, oleanolic acid, and ursolicacid are each present in an amount of 0.01-50 g/L, preferably 0.1-30g/L, preferably 0.5-20 g/L, preferably 1-15 g/L, preferably 2-10 g/L,preferably 4-7 g/L, relative to a total volume of the formulation.

In one or more embodiments, the pharmaceutically acceptable carrierand/or excipient is at least one selected from the group consisting ofan organic solvent, a buffer, an inorganic salt, a fatty acid, avegetable oil, a synthetic fatty ester, a surfactant, and a polymer.

Suitable organic solvents are as previously specified. In a preferredembodiment, the pharmaceutically acceptable carrier and/or excipientincludes DMSO. If present, the organic solvent may be present in theformulation in an amount of 1-1,000 g/L, 10-750 g/L, 25-500 g/L, 50-250g/L, or 100-200 g/L.

Exemplary buffers include, but are not limited to, phosphate buffers,citrate buffer, acetate buffers, borate buffers, carbonate buffers,bicarbonate buffers, and buffers with other organic acids and salts.

Exemplary inorganic salts include, but are not limited to, calciumcarbonate, calcium phosphate, disodium hydrogen phosphate, potassiumhydrogen phosphate, sodium chloride, zinc oxide, zinc sulfate, andmagnesium trisilicate.

Exemplary fatty acids include, but are not limited to, an omega-3 fattyacid (e.g., linolenic acid, docosahexaenoic acid, eicosapentaenoic acid)and an omega-6 fatty acid (e.g., linoleic acid, eicosadienoic acid,arachidonic acid). Other fatty acids, such as oleic acid, palmitoleicacid, palmitic acid, stearic acid, and myristic acid, may be included.

Exemplary vegetable oils include, but are not limited to, avocado oil,olive oil, palm oil, coconut oil, rapeseed oil, soybean oil, corn oil,sunflower oil, cottonseed oil, and peanut oil, grape seed oil, hazelnutoil, linseed oil, rice bran oil, safflower oil, sesame oil, brazil nutoil, carapa oil, passion fruit oil, and cocoa butter.

Exemplary synthetic fatty esters include, without limitation, methyl,ethyl, isopropyl and butyl esters of fatty acids (e.g., isopropylpalmitate, glyceryl stearate, ethyl oleate, isopropyl myristate,isopropyl isostearate, diisopropyl sebacate, ethyl stearate, di-n-butyladipate, dipropylene glycol pelargonate), C₁₂-C₁₆ fatty alcohol lactates(e.g., cetyl lactate and lauryl lactate), propylene dipelargonate,2-ethylhexyl isononoate, 2-ethylhexyl stearate, isopropyl lanolate,2-ethylhexyl salicylate, cetyl myristate, oleyl myristate, oleylstearate, oleyl oleate, hexyl laurate, isohexyl laurate, propyleneglycol fatty ester, and polyoxyethylene sorbitan fatty ester. As usedherein, the term “propylene glycol fatty ester” refers to a monoether ordiester, or mixtures thereof, formed between propylene glycol orpolypropylene glycol and a fatty acid. The term “polyoxyethylenesorbitan fatty ester” denotes oleate esters of sorbitol and itsanhydrides, typically copolymerized with ethylene oxide.

Surfactants may act as detergents, wetting agents, emulsifiers, foamingagents, and dispersants. Surfactants that may be present in thecompositions of the present disclosure include zwitterionic (amphoteric)surfactants, e.g., phosphatidylcholine, and3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS),anionic surfactants, e.g., sodium lauryl sulfate, sodium octanesulfonate, sodium decane sulfonate, and sodium dodecane sulfonate,non-ionic surfactants, e.g., sorbitan monolaurate, sorbitanmonopalmitate, sorbitan trioleate, polysorbates such as polysorbate 20(Tween 20), polysorbate 60 (Tween 60), and polysorbate 80 (Tween 80),cationic surfactants, e.g., decyltrimethyl ammonium bromide,dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide,tetradecyltrimethyl-ammonium chloride, and dodecylammonium chloride, andcombinations thereof.

Exemplary polymers include, without limitation, polylactides,polyglycolides, polycaprolactones, polyanhydrides, polyurethanes,polyesteramides, polyorthoesters, polydioxanones, polyacetals,polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes,polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates,polyalkylene succinates, poly(malic acid), poly(maleic anhydride), apolyvinyl alcohols, and copolymers, terpolymers, or combinations ormixtures therein. The copolymer/terpolymer may be a randomcopolymer/terpolymer, or a block copolymer/terpolymer.

Depending on the route of administration e.g. oral, parental, ortopical, the formulation may be in the form of solid dosage form such astablets, caplets, capsules, powders, and granules, semi-solid dosageform such as ointments, creams, lotions, gels, pastes, andsuppositories, liquid dosage forms such as solutions, and dispersions,inhalation dosage form such as aerosols, and spray, or transdermaldosage form such as patches.

In a preferred embodiment, the formulation containing the mixture ofcorosolic acid, oleanolic acid, and ursolic acid is intended for topicalapplication and it may further contain the emulsifier, the emollient,and the occlusive agent as described in the first aspect. If present,the emulsifier may be present in the formulation in an amount of 1-100g/L, 5-80 g/L, 10-60 g/L, or 15-30 g/L. If present, the emollient may bepresent in the plant-based composition in an amount of 1-100 g/L, 5-80g/L, 10-60 g/L, or 15-30 g/L. If present, the occlusive agent may bepresent in the plant-based composition in an amount of 1-100 g/L, 5-80g/L, 10-60 g/L, or 15-30 g/L. Topical administration may involve the useof transdermal administration such as transdermal patches oriontophoresis devices. Formulation of drugs is discussed in, forexample, Hoover, J. E. Remington's pharmaceutical sciences, MackPublishing Co., Easton, Pa., 1975; and Liberman, H. A.; Lachman, L.,Eds. Pharmaceutical dosage forms, Marcel Decker, New York, N.Y., 1980,which are incorporated herein by reference in their entirety. In someembodiments, the formulation may be formulated for oral administration.

Another aspect of the present disclosure relates to a method fortreating a skin disease or condition. The method involves topicallyadministering an effective amount of the plant-based composition or theformulation containing the mixture of corosolic acid, oleanolic acid,and ursolic acid onto a subject in need of therapy. In one or moreembodiment, the skin disease or condition is at least one selected fromthe group consisting of warts, corns, calluses, umbilical granulomas,and superficial basal cell carcinoma.

Hyperkeratotic tissues such as corns (heloma), calluses (tyloma) andwarts (condyloma) are well defined, thickened lesions of the epidermis.Pain produced by the thickened tissue can cause these lesions to bedebilitating.

Corns (heloma) and calluses (tyloma) may occur at skin sites that areinvolved in chronic mechanical stress. Corns are found on skin surfaces,principally on the dorsal surface of toes or fingers and between toes.Corns can be painful when pressed. A hard corn (Heloma durum) is ahyperkeratotic lesion which appears over a bony prominence and may havea deep nucleus. A soft corn (Heloma molle) is a hyperkeratotic lesionwhich is frequently found between adjacent toes. A callus may be adiffuse or circumscribed area of hyperkeratosis at a site of repeatedpressure and friction. Calluses may be found on the soles of feet,especially metatarsal heads, as well as palms and knees. Calluses arenot necessarily painful.

Warts may be caused by skin infection with Human papillomavirus (HPV).Once developed, warts can be spread to other parts of the body or toother persons through skin-to-skin contact or contact with a surfacecontaminated with HPV. Warts are more commonly diagnosed based on theirphysical appearances and locations on the body. Various types of warthave been classified by their clinical presentation (e.g. shape, siteaffected), as well as the type of human papillomavirus involved. Commonwart (Verruca vulgaris) is a domed, irregularly surfaced lesion thatdisplays hyperkeratosis and may occur, most often on fingers or hands.Periungual wart is a cauliflower-like cluster of warts occur on the skinaround finger and toe nails. Flat wart (Verruca plana) is a small,smooth wart that usually occurs on the face, neck, hands, wrists andknees. Flat warts are most common on the faces and extremities ofchildren and on the lower legs of women. Plantar wart (Verrucaplanlaris) a hard, sometimes painful lump that is usually only found onthe soles of the feet. Plantar warts are often observed with multipleblack specks in the center and become callused and grow into the footdue to the forces exerted on the foot from everyday movement. Plantarwarts may often be associated with pain.

Umbilical granuloma is a common umbilical abnormality in infants,causing inflammation and drainage. It presents as soft, moist, pinkfriable lesion on a baby's belly button. It usually appears after theumbilical cord has been cut. It is also possible for an adult to developan umbilical granuloma.

Basal cell carcinoma (BCC), also known as basal cell cancer, is a commontype of skin cancer. BCC often appears as a painless raised area ofskin, which may be a shiny, pearly skin nodule. BCC most often affectsthe skin of head, neck, and trunk that are exposed to the sun.Superficial basal cell carcinoma, formerly referred to in-situ basalcell carcinoma, is characterized by a superficial proliferation ofneoplastic basal cells.

As used herein, the terms “treat”, “treatment”, and “treating” in thecontext of the administration of the composition to a subject in needthereof refer to the reduction or inhibition of the progression and/orduration of a disease, the reduction or amelioration of the severity ofthe disease, and/or the amelioration of one or more symptoms thereofresulting from the administration the composition. “Treating” or“treatment” of the disease includes preventing the disease fromoccurring in a subject that may be predisposed to the disease but doesnot yet experience or exhibit symptoms of the disease (prophylactictreatment), inhibiting the disease (slowing or arresting itsdevelopment), ameliorating the disease, providing relief from thesymptoms or side-effects of the disease, and relieving the disease(causing regression of the disease). With regard to the disease orcondition, these terms simply mean that one or more of the symptoms ofthe disease or condition will be reduced. Such terms may refer to one,two, three, or more results following the administration of thecomposition: (1) a stabilization, reduction (e.g. by more than 10%, 20%,30%, 40%, 50%, preferably by more than 60% of the size of a callus or acorn relative to its initial size before administration), or eliminationof the symptoms (e.g. removal of a wart), (2) inhibiting the growth ofpathogens (e.g. HPV), (3) relieving to some extent one or more symptomsassociated with the disease or condition (e.g. reduction in pain,redness, bumpiness, swelling, and/or oozing associated with warts andumbilical granuloma), (4) an increase in disease-free, relapse-free,progression-free duration, or rate, (5) a decrease in hospitalizationrate, and (6) a decrease in hospitalization length.

The term “subject in need of therapy”, “subject”, and “patient” are usedinterchangeably. As used herein, they refer to any subject for whom orwhich therapy, including with the according to the present disclosurecompositions (e.g. the plant-based composition, the formulationcontaining the mixture of corosolic acid, oleanolic acid, and ursolicacid) is desired. In most embodiments, the subject is a mammal,including but not limited to a human, a non-human primate such as achimpanzee, a domestic livestock such as a cattle, a horse, a swine, apet animal such as a dog, a cat, and a rabbit, and a laboratory subjectsuch as a rodent, e.g. a rat, a mouse, and a guinea pig. In preferredembodiments, the subject is a human. In some embodiment, the subject isan infant.

The method involves topically administering an effective amount of theplant-based composition or the formulation containing the mixture ofcorosolic acid, oleanolic acid, and/or ursolic acid onto the subject. Insome embodiments, the subject is administered with an effective amountof the plant-based composition or the formulation at least once daily, 2to 10 times daily, or 3 to 5 times daily for at least 1 day, 2 to 30consecutive days, 5 to 21 consecutive days, or 7 to 14 consecutive days.During administration, the plant-based composition or the formulationmay be applied, rubbed, and/or spread onto the desired/affected area ofskin. Preferably, the desired/affected area of skin is cleaned prior toadministration.

The terms “effective amount”, “therapeutically effective amount”, or“pharmaceutically effective amount” refer to that amount of thecomposition being administered which will relieve to some extent one ormore of the symptoms of the disease being treated. The result can bereduction and/or alleviation of the signs, symptoms, or causes of adisease, or any other desired alteration of a biological system. Theamount will vary with the condition being treated and the concentrationof the active ingredients (e.g. the alcohol extract of at least onespecies of Tecoma, the mixture of corosolic acid, oleanolic acid, and/orursolic acid) present in the formulation being administered. Appropriateamounts in any given instance will be readily apparent to those ofordinary skill in the art by routine experimentation.

Experiments were carried out which evaluate the effectiveness of theplant-based composition and the formulation containing the mixture ofcorosolic acid, oleanolic acid, and ursolic acid on treating warts (seeFIGS. 2A-C, 3A-C, and 4A-C), corns and calluses (see FIGS. 5A-B, and6A-B) and umbilical granuloma (see FIGS. 7A-B). It is worth noting thatthe combination of three acids, namely corosolic acid, oleanolic acid,and ursolic acid, has a synergistic effect for treatment of theaforementioned skin lesions compared to topical application of only oneacid among the three (see Example 1).

The compositions and formulations of the present disclosure may also beused in the treatment of hyperkeratinizing and hyperproliferative skindiseases and conditions including, but not limited to, melanoma, basalcell carcinoma (BCC), psoriasis, viral infection caused by the herpessimplex virus (e.g. cold sores), nail deformations (e.g. ingrowntoenails), mouth ulcers (canker sores), ichthyoses, porokeratoses,follicular keratoses, palmoplantar keratodermas, eczema, acne, dandruff,and dry skin.

A further aspect of the present disclosure relates to a personal careproduct comprising the plant-based composition or thecomposition/formulation containing the mixture of corosolic acid,oleanolic acid, and ursolic acid. As used herein, the term “care” refersto the improvement and/or the maintenance of the qualities of the skin.These qualities are subject to improvement and/or are maintained throughcare of the skin both in healthy subjects as well as those which presentdiseases and/or conditions of the skin, such as and not restricted to,warts, corns, calluses, umbilical granulomas, and superficial basal cellcarcinoma. Exemplary personal care products include plasters, bandages,patches, wound healing ointments, sunscreens, body lotions, facialcreams, body wash, facial wash, bar soap, liquid soap (e.g., hand soap),hand sanitizer (including rinse off and leave-on and aqueous-based handdisinfectants), antiperspirants, deodorants, shampoos, infant careproducts (e.g. infant body lotions, creams, and body washes), dentalcare products such as toothpastes and mouth wash.

The examples below are intended to further illustrate protocols forpreparing, characterizing the plant-based composition as well as thecomposition/formulation containing the mixture of corosolic acid,oleanolic acid, and ursolic acid, and uses thereof, and are not intendedto limit the scope of the claims.

Example 1 Experimental

Initial steps involved extracting Tecoma stans leaves with methanol orethanol alcohol. Then, the extract was obtained via evaporating thealcohol and re-suspending the dry matter in pure DMSO(dimethylsulphoxide) at a concentration of 20 mg/mL DMSO. Importantly,active ingredients were found mainly in the leaves of the plant, andonly minimum curing effect was found using ethanolic or methanolicextract from Tecoma stans flowers, roots, or fruit (also known as pods).Stem and bark of Tecoma stans showed only very minor therapeutic effectcompared to the leaf extract (20%).

As disclosed herein, 14 compounds have been isolated from dry leaves ofTecoma stans, four of which are known for their antidiabetic effect andability to reduce the glycemic index. After identifying the 14 compoundsin the methanolic extract from the dry leaves, each compound wasindependently tested on human skin warts.

A minor curing effect was observed by applying corosolic acid (FIG. 1I).Therefore, corosolic acid was mixed with its two related compounds,namely oleanolic acid (FIG. 1E) and ursolic acid (FIG. 1F), isolatedfrom the same extract. Compositions containing a mixture of these threecompounds were prepared by mixing the compounds in an ointment at aconcentration of 1 mg/gm of each compound per a total weight of theointment, emulsifying the compounds in a lotion base at a concentrationof 0.1 mg/mL of each compound per a total volume of the lotion, orsuspending three compounds together in DMSO at a concentration of 1mg/mL of each compound per a total volume of DMSO. The compositions wereapplied topically twice a day to the desired skin area as indicated ineach case (see FIGS. 3A-C, 4A-C, 5A-B).

Compositions containing the mixture of corosolic acid, oleanolic acid,and ursolic acid were able to cure skin warts, with an efficacy that wasonly about 10% less than that of the crude methanolic extract of Tecomastans leaves. Therefore, a combination of the three compounds includingoleanolic acid, ursolic acid, and corosolic acid played a major role inthe anti-wart activity of Tecoma stans. It is important to note thatnone of the three compounds showed anti-wart activity alone thatexceeded 10% of the crude methanol extract. Accordingly, obtaining 90%effectiveness rate of the crude methanol extract by combining corosolicacid, oleanolic acid, and ursolic acid indicated a synergistic curingeffect among the three compounds. It is also important to note thatmixing the three compounds together in DMSO yielded faster therapeuticresults than the topical cream that contained same concentrations of thethree compounds. Similarly, three other structurally relatedheterocyclic compounds were tested for their ability to kill variousmelanoma cell lines by induction of apoptosis.

Example 2 Results and Discussions

Our experimental data showed that certain extracts prepared from Tecomastans as well as some of its isolated and characterized compounds wereable to treat skin warts, skin callus, skin corns and umbilicalgranulomas.

Interestingly, when the crude extracts and certain combinations of theisolated 14 compounds (see FIGS. 1A-N) were used as topical ointments,they were able to effectively cure skin warts, callus, and corns withoutsigns of recurrence, indicating that they were able to eradicate thecausative papilloma virus. Specifically, mixtures of three naturalheterocyclic compounds (i.e. corosolic acid, oleanolic acid, and ursolicacid) which were isolated from a Tecoma stans plant have been shown toeffectively treat skin wart, callus, corns, and umbilical granuloma.These compounds are harmless on humans, and cause no skin irritations.

In addition, the experimental data of treating umbilical granuloma usingextracts from Tecoma stans showed effective removal of the granulomawithin two days using the topical application twice per day. It is worthnoting that neither the tested extracts nor the pure compounds isolatedfrom Tecoma stans caused any skin reaction or left any scar on theentire group of tested subjects. These data indicated that extracts fromTecoma stans and its purified and identified compounds were effectivefor treating skin wars, callus, corn, and umbilical granuloma.Furthermore, the data demonstrated that the extract from Tecoma stansmight be used to treat herpes simplex virus including type 1 (HSV-1) andtype 2 (HSV-2). Therefore, these data collectively indicated thatextracts from Tecoma stans contain therapeutic compounds with antiviralactivity (including anti-HSV-1, anti-HSV-2, and anti-papilloma virusactivities).

Example 3 Clinical Impact

Based on the above, this disclosure provides natural crude extracts aswell as isolated compounds from Tecoma stans and potentially otherTecoma species useful for treating skin warts, skin callus, skin corns,and umbilical granulomas, potentially for treating genital warts andsuperficial basal cell carcinomas, and being applied as an antiviralagent for treating papilloma virus and HSV-1 and HSV-2 viruses.

1: A plant-based composition, comprising: 1-500 g/L of an alcoholextract of at least one species of Tecoma relative to a total volume ofthe plant-based composition; and an exogenous pharmaceuticallyacceptable carrier and/or excipient which is not present in the at leastone species of Tecoma, wherein the exogenous pharmaceutically acceptablecarrier and/or excipient is an organic solvent, a cream base, or both,with the proviso that the organic solvent is not a polar protic solvent.2: The plant-based composition of claim 1, wherein the at least onespecies of Tecoma is selected from the group consisting of Tecomaheckii, Tecoma capensis, Tecoma castanifolia, Tecoma cochabambensis,Tecoma fulva, Tecoma nyassae, Tecoma rosifolia, Tecoma stans, Tecomatenuiflora, and Tecoma weberbaueriana. 3: The plant-based composition ofclaim 2, wherein the at least one species of Tecoma is Tecoma stans. 4:The plant-based composition of claim 1, wherein the exogenouspharmaceutically acceptable carrier and/or excipient is the cream base,and wherein the cream base comprises at least one selected from thegroup consisting of an emollient, an occlusive agent, and a thickener.5: The plant-based composition of claim 1, wherein the exogenouspharmaceutically acceptable carrier and/or excipient is DMSO. 6: Theplant-based composition of claim 1, wherein the alcohol extract of atleast one species of Tecoma is sourced from a leaf, a stem, and/or abark. 7: The plant-based composition of claim 1, wherein the alcoholextract of at least one species of Tecoma is sourced from a leaf. 8: Theplant-based composition of claim 1, wherein the alcohol extract of atleast one species of Tecoma is a methanol extract, an ethanol extract,or both. 9: The plant-based composition of claim 1, comprising 10-100g/L of an alcohol extract of Tecoma stans relative to a total volume ofthe plant-based composition. 10: A composition, comprising: corosolicacid; oleanolic acid; and ursolic acid; wherein: a weight ratio ofcorosolic acid to oleanolic acid is in a range of 1:2 to 2:1; a weightratio of corosolic acid to ursolic acid is in a range of 1:2 to 2:1; anda total weight of corosolic acid, oleanolic acid, and ursolic acid is atleast 50 wt % relative to a total weight of the composition. 11: Aformulation, comprising: the composition of claim 10; and apharmaceutically acceptable carrier and/or excipient, wherein corosolicacid, oleanolic acid, and ursolic acid are each present in an amount of0.01-50 g/L relative to a total volume of the formulation. 12: Theformulation of claim 11, wherein the pharmaceutically acceptable carrierand/or excipient comprises DMSO. 13: A method for treating a skindisease or condition, the method comprising topically administering aneffective amount of the plant-based composition of claim 1 onto asubject in need of therapy. 14: The method of claim 13, wherein the skindisease or condition is at least one selected from the group consistingof warts, corns, calluses, umbilical granulomas, and superficial basalcell carcinoma. 15: The method of claim 13, wherein the subject isadministered with an effective amount of the plant-based composition 1to 10 times daily for 1 to 30 consecutive days. 16: A method fortreating a skin disease or condition, the method comprising topicallyadministering an effective amount of the formulation of claim 11 onto asubject in need of therapy. 17: The method of claim 16, wherein the skindisease or condition is at least one selected from the group consistingof warts, corns, calluses, umbilical granulomas, and superficial basalcell carcinoma. 18: The method of claim 16, wherein the subject isadministered with an effective amount of the formulation 1 to 10 timesdaily for 1 to 30 consecutive days. 19: A personal care product,comprising the plant-based composition of claim
 1. 20: A personal careproduct, comprising the composition of claim 10.